Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Clinics |
Texto Completo: | https://www.revistas.usp.br/clinics/article/view/154888 |
Resumo: | The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis. |
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Clinics |
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Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesisInsulin Receptor SubstrateAdaptor ProteinSignal TransductionHematopoiesisLeukemiaMyeloproliferative NeoplasmsThe insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis.Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo2019-02-18info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/clinics/article/view/15488810.6061/clinics/2018/e566sClinics; Vol. 73 No. Suppl. 1 (2018); e566sClinics; v. 73 n. Suppl. 1 (2018); e566sClinics; Vol. 73 Núm. Suppl. 1 (2018); e566s1980-53221807-5932reponame:Clinicsinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/clinics/article/view/154888/150805Copyright (c) 2019 Clinicsinfo:eu-repo/semantics/openAccessMachado-Neto, João AgostinhoFenerich, Bruna AlvesAlves, Ana Paula Nunes RodriguesFernandes, aqueline CristinaScopim-Ribeiro, RenataCoelho-Silva, Juan LuizTraina, Fabiola2019-05-14T11:48:25Zoai:revistas.usp.br:article/154888Revistahttps://www.revistas.usp.br/clinicsPUBhttps://www.revistas.usp.br/clinics/oai||clinics@hc.fm.usp.br1980-53221807-5932opendoar:2019-05-14T11:48:25Clinics - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
title |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
spellingShingle |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis Machado-Neto, João Agostinho Insulin Receptor Substrate Adaptor Protein Signal Transduction Hematopoiesis Leukemia Myeloproliferative Neoplasms |
title_short |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
title_full |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
title_fullStr |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
title_full_unstemmed |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
title_sort |
Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis |
author |
Machado-Neto, João Agostinho |
author_facet |
Machado-Neto, João Agostinho Fenerich, Bruna Alves Alves, Ana Paula Nunes Rodrigues Fernandes, aqueline Cristina Scopim-Ribeiro, Renata Coelho-Silva, Juan Luiz Traina, Fabiola |
author_role |
author |
author2 |
Fenerich, Bruna Alves Alves, Ana Paula Nunes Rodrigues Fernandes, aqueline Cristina Scopim-Ribeiro, Renata Coelho-Silva, Juan Luiz Traina, Fabiola |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Machado-Neto, João Agostinho Fenerich, Bruna Alves Alves, Ana Paula Nunes Rodrigues Fernandes, aqueline Cristina Scopim-Ribeiro, Renata Coelho-Silva, Juan Luiz Traina, Fabiola |
dc.subject.por.fl_str_mv |
Insulin Receptor Substrate Adaptor Protein Signal Transduction Hematopoiesis Leukemia Myeloproliferative Neoplasms |
topic |
Insulin Receptor Substrate Adaptor Protein Signal Transduction Hematopoiesis Leukemia Myeloproliferative Neoplasms |
description |
The insulin receptor substrate (IRS) proteins are a family of cytoplasmic proteins that integrate and coordinate the transmission of signals from the extracellular to the intracellular environment via transmembrane receptors, thus regulating cell growth, metabolism, survival and proliferation. The PI3K/AKT/mTOR and MAPK signaling pathways are the best-characterized downstream signaling pathways activated by IRS signaling (canonical pathways). However, novel signaling axes involving IRS proteins (noncanonical pathways) have recently been identified in solid tumor and hematologic neoplasm models. Insulin receptor substrate-1 (IRS1) and insulin receptor substrate-2 (IRS2) are the best-characterized IRS proteins in hematologic-related processes. IRS2 binds to important cellular receptors involved in normal hematopoiesis (EPOR, MPL and IGF1R). Moreover, the identification of IRS1/ABL1 and IRS2/JAK2V617F interactions and their functional consequences has opened a new frontier for investigating the roles of the IRS protein family in malignant hematopoiesis. Insulin receptor substrate-4 (IRS4) is absent in normal hematopoietic tissues but may be expressed under abnormal conditions. Moreover, insulin receptor substrate-5 (DOK4) and insulin receptor substrate-6 (DOK5) are linked to lymphocyte regulation. An improved understanding of the signaling pathways mediated by IRS proteins in hematopoiesis-related processes, along with the increased development of agonists and antagonists of these signaling axes, may generate new therapeutic approaches for hematological diseases. The scope of this review is to recapitulate and review the evidence for the functions of IRS proteins in normal and malignant hematopoiesis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-02-18 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/154888 10.6061/clinics/2018/e566s |
url |
https://www.revistas.usp.br/clinics/article/view/154888 |
identifier_str_mv |
10.6061/clinics/2018/e566s |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/clinics/article/view/154888/150805 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2019 Clinics info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2019 Clinics |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
publisher.none.fl_str_mv |
Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo |
dc.source.none.fl_str_mv |
Clinics; Vol. 73 No. Suppl. 1 (2018); e566s Clinics; v. 73 n. Suppl. 1 (2018); e566s Clinics; Vol. 73 Núm. Suppl. 1 (2018); e566s 1980-5322 1807-5932 reponame:Clinics instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Clinics |
collection |
Clinics |
repository.name.fl_str_mv |
Clinics - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
||clinics@hc.fm.usp.br |
_version_ |
1800222764076892160 |